A team at the governmental scientific research institute Riken on Sept. 12 transplanted a retina sheet made of induced pluripotent stem (iPS) cells into a woman — the world’s first clinical research involving the transplant of human iPS cells. The surgery represents an important step that may lead to the application of iPS cells in the treatment of disease. Since iPS cells are touted as a powerful tool in the field of regenerative medicine, the world will pay attention to the results of the Riken team’s transplant.
Still, it must not be forgotten that the main purpose of this clinical research should be to confirm the safety of the transplant. Instead of trying to quickly obtain conclusions from the transplant, researchers and other parties concerned should calmly evaluate the clinical test results in a multi-faceted manner. This process will be indispensable in making regenerative medicine reliable and effective.
In 2007, Kyoto University professor Shinya Yamanaka developed iPS cells that could grow into any type of tissue in the human body by adding four genes to mature skin cells. Because iPS cells have applications in regenerative medicine and in the development of new drugs, his research won him the 2012 Nobel Prize in Physiology or Medicine, which he shared with fellow researcher John Gurdon.
The transplant on Sept. 12 was carried out at the Institute of Biomedical Research and Innovation Hospital in Kobe by a team led by Masayo Takahashi, an ophthalmologist with the Riken Center for Developmental Biology.
The patient, a woman in her 70s from Hyogo Prefecture, is suffering from age-related macular degeneration in the exudative form, a condition that may cause a sudden loss of vision due to retinal damage. The eye disease is characterized by the accumulation of abnormal, fragile blood vessels in the retina. Bleeding from them damages the macula or the yellow spot in the center of a visual field. As a result, things seen in the center of a visual field appear deformed or blackened. In the worst case, patients can go blind. About 700,000 Japanese are estimated to have the disease.
The Riken team extracted skin cells from the patient, created iPS cells by introducing genes, developed them into a layer of cells known as pigment epithelium and then created a retinal sheet to be used in the transplant. After removing abnormal blood vessels and injured tissue from the retina of her right eye, the team transplanted the retinal sheet into that eye.
The patient had received injections as treatment for three years, but her eye condition gradually worsened. She cannot see anything in the center of her visual field and her eyesight is less than 0.1 even with the help of glasses.
Given the seriousness of her macular degeneration, it is not expected that her eyesight will greatly improve. It is believed that the condition of her eye one year after the transplant will determine whether the clinical research has been successful.
The Riken team thinks that if the patient is at least liberated from the need to rely on injections, and if the functions of the eye are maintained, she will experience significant benefit from the procedure. Although the team plans to carry out the same procedure on five more patients, it has not yet worked out a schedule.
It is remarkable that iPS cells have been used for clinical research for just seven years since Yamanaka created iPS cells in 2007 by using human skin cells. In the early stage of his research in 2006 he had created iPS cells by using skin cells taken from a mouse.
This rapid progress was made possible by researchers’ strenuous efforts and strong support from the government. Still, sufficient research data on iPS cells has yet to be gathered, and there are a number of aspects concerning iPS cells that remain unexplained.
The most important thing about the clinical test is to find out whether the iPS cells used in the transplant will become carcinogenic and whether unexpected changes will occur to the cells.
In theory iPS cells should not cause rejection, but that needs to be proven. There could also be as yet unknown risks in the clinical test. It is desirable that researchers on the Riken team publish, at an early date, scientific papers containing relevant data, including on the quality of the transplanted cells, so that the test can be checked from various angles.
Full information disclosure and careful examination of the results of the clinical test are indispensable.
Takahashi and others think that it will take more than 10 years before iPS cells can be used for actual treatment of disease. Even if their safety and effectiveness are confirmed through clinical tests, a lot of time and money will be needed for their application for treatment of diseases.
In the case of the latest clinical test, it took the Riken team four months to develop iPS cells from the patient’s skin and six more months to create the retina sheet. The endeavor cost tens of millions of yen.
Yamanaka and other researchers at Kyoto University are pushing a plan to stock a large amount of iPS cells in advance to reduce the time and money needed for their clinical application. But it is not known whether this scheme will solve the problems.
Although iPS cells have a great potential, it would be unwise to rely on them alone. It will be necessary to nurture research in other areas of regenerative medicine as well.
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